AB1453 INFLAMMATION MARKERS, SYSTEMIC INFLAMMATORY BASED SCORES (SIBS) AND CYTOKINE PROFILES IN ADULT CHRONIC NONBACTERIAL OSTEOMYELITIS (CNO)/SAPHO SYNDROME: AN IMMUNOLOGICAL CHARACTERIZATION
Authors: A. Leerling, E. Andeweg, J. Faber, T. Streefland, O. Dekkers, N. Appelman-Dijkstra, E. Winter
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Chronic non-bacterial osteomyelitis (CNO) is a rare bone disease occurring in children and adults. Adults mainly present with osteitis and hyperostosis of the anterior chest wall, sometimes occurring in the context of synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome [1]. CNO is hypothesized to be an auto-inflammatory disease, as studies on pediatric patients have shown raised erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and elevated serum concentrations of interleukin (IL)-6, 8, 17A and TNF-a [2]. For adults, however, the suspected systemic immune activation is not consistently reflected by these generic markers, and data on cytokine expression are scarce and variable [3, 4]. <h3>Objectives</h3> To provide broad immunological characterization of adult CNO/SAPHO, including cytokine profiles, compared to controls. <h3>Methods</h3> Cross-sectional study in our CNO referral center including adult CNO/SAPHO patients with active disease (n=172) and controls (n=82) referred between 1992-2022 not using immunomodulatory treatment (exempting NSAIDs) or bisphosphonates. Generic inflammation parameters and systemic inflammatory based scores (SIBS) were compared between patients and controls and between patients with and without concomitant arthritis/dermatitis, and with strong or moderate increase in isotope uptake on nuclear imaging. Serum levels of Th1/2 and Th17-derived cytokines were determined with electrochemiluminescent immunoassays, and receptor activator of nuclear factor kappa beta (RANKL) and osteoprotegerin (OPG) with ELISA in 33 patients and 8 controls. <h3>Results</h3> ESR, CRP, platelet, leucocyte and neutrophil count were higher in CNO/SAPHO patients than in controls, but generally remained within the reference range. ESR was also higher in patients with concomitant arthritis/dermatitis compared to isolated osteitis (24 versus 16, <i>p=0.009</i>), and in patients with strongly rather than moderately increased isotope uptake on nuclear imaging (20 versus 13, <i>p= 0.009</i>). Neutrophil-derived SIBS (neutrophil/lymphocyte ratio (NLR) and systemic immune inflammation index (product of NLR and platelet count)) were elevated in CNO patients compared to controls. Cytokine analyses revealed no differential expression for IL-6, -8, -10, -13, -17A, -22, -23, -27, TNF-a, IFN-γ, and MIP-3a, nor for the bone markers RANKL and osteoprotegerin. <h3>Conclusion</h3> In this adult CNO/SAPHO cohort, generic inflammation markers and neutrophil-derived SIBS NLR and SII were increased compared to controls. In contrast to previous studies, we found no differential expression of IL-6, -8, -17A and TNF-a to support systemic cytokine imbalance in adult CNO/SAPHO. Further studies are needed to evaluate whether the auto-inflammatory hypothesis in CNO/SAPHO applies as much to the adult as pediatric subtype, and if so, whether the local inflammasome is systemically reflected. <h3>References</h3> [1]Leerling A, Dekkers O, Appelman-Dijkstra N, Winter E. Clinical and therapeutic diversity in adult chronic nonbacterial osteomyelitis (CNO) of the sternocostoclavicular region: a meta-analysis. Rheumatology (Oxford). 2022. [2]Buch K, Thuesen ACB, Brons C, Schwarz P. Chronic Non-bacterial Osteomyelitis: A Review. Calcified Tissue International. 2019;104(5):544-53. [3]Zhang S, Li C, Zhang S, Li L, Zhang W, Dong Z, et al. Serum levels of proinflammatory, anti-inflammatory cytokines, and RANKL/OPG in synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. Modern rheumatology. 2019;29(3):523-30. [4]Przepiera-Bedzak H, Fischer K, Brzosko M. Serum IL-6 and IL-23 Levels and Their Correlation with Angiogenic Cytokines and Disease Activity in Ankylosing Spondylitis, Psoriatic Arthritis, and SAPHO Syndrome. Mediators Inflamm. 2015;2015(2):785705-7. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.